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  • 1
    ISSN: 1432-0533
    Keywords: Key words Stem cell ; Tumor ; Malformation ; Epilepsy ; Ganglioglioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The etiology and pathogenesis of complex focal lesions associated with chronic, intractable epilepsy are largely unknown. Some data indicate that malformative changes of the central nervous system may preceed the development of gangliogliomas and other epilepsy-associated neoplasms. In the present immunhistochemical study, we have examined epilepsy-associated lesions for CD34, a stem cell marker transiently expressed during early neurulation. Surprisingly, most tissue samples from patients with chronic epilepsy (n = 262) revealed neural cells immunoreactive for CD34. Prominent immunoreactivity was detected in gangliogliomas (74%), low-grade astrocytomas (62%) and oligodendrogliomas (59%). Only 52% of non-neoplastic, malformative pathologies, such as glio-neuronal hamartias or hamartomas showed solitary or small clusters of CD34-immunoreactive cells. None of the adult control tissues (n = 22), none of the specimens obtained from the developing human brain (n = 44) and none of those tumor samples from patients without epilepsy (n = 63) contained CD34-immunoreactive neural cells. However, a malignant teratoma with microscopic features of early neural differentiation displayed a focal CD34-immunoreactive staining pattern. The majority of CD34-immunoreactive cells co-localized with S-100 protein and a small subpopulation was also immunoreactive for neuronal antigens. CD34 may, thus, represent a valuable marker for the diagnostic evaluation of neoplastic and/or malformative pathological changes in epilepsy patients. The CD34 immunoreactivity of these lesions indicates an origin from dysplastic or atypically differentiated neural precursors. Further studies may elucidate the functional significance of CD34 expression during the pathogenesis of epilepsy-related focal lesions as well as during neurogenesis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Key words Chromosome 9 ; Chromosome 16 ; Epilepsy ; Hamartoma ; Pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glioneuronal malformations with a striking histological resemblance to cortical tubers of tuberous sclerosis, but no extracerebral stigmata of this phacomatosis, are frequently encountered in patients with chronic pharmacoresistant epilepsies. It is controversial as to whether these lesion represent a forme fruste of tuberous sclerosis or a distinct entity. The recently reported loss of heterozygosity (LOH) at the regions of the TSC1 or TSC2 locus in hamartomas obtained from different organs of patients with established tuberous sclerosis, including cortical tubers, stimulated us to examine epilepsy-associated tuberous sclerosis-like glioneuronal malformations with respect to LOH at the TSC1 and TSC2 loci of chromosomes 9q34 and 16p13.3, respectively. The analysis was carried out on DNA derived from paraffin-embedded brain tissues of 11 patients. For 5 patients, peripheral blood leukocytes were also available for DNA extraction. We performed microsatellite analysis with five markers on chromosome 9 and four markers on chromosome 16. In addition, polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis was performed using a polymorphic EcoRV restriction site in exon 40 of the TSC2 gene. No LOH was identified in any of the cases. These findings do not support a relationship between the epilepsy-associated glioneuronal lesions and tuberous sclerosis. However, tuberous sclerosis is genetically heterogeneous and microsatellite and RFLP analysis cannot exclude small deletions or point mutations. Thus, given the histopathological similarity of glioneuronal malformations in epilepsy patients to cortical tubers, further molecular genetic studies will be needed as our understanding of the molecular basis of tuberous sclerosis increases to completely clarify the relationship of these lesions to tuberous sclerosis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7373
    Keywords: ECR expression ; glioblastoma ; melanoma ; serum free medium ; migration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Local tumor invasion into the surrounding brain tissue is a major characteristic of malignant gliomas. These processes critically depend on the interaction of tumor cells with various extracellular matrix (ECM) components. Because only little quantitative information about expression of ECM gene products in general and expression in response to alterations of the surrounding environment is available, the present study was designed. Four human glioblastoma cell lines (U373MG, U138MG, U251MG, GaMG) as well as four human melanoma cell lines (MV3, BLM, 530, IF6) were tested with semiquantitative RT-PCR for their ability to express mRNA of different human ECM components (fibronectin, decorin, tenascin, collagen I, collagen IV, versican). In addition, two human medulloblastoma (MHH-Med 1, MHH-Med 4) and two fibrosarcoma (HT1080, U2OS) cell lines were analyzed. Cells which were grown in DMEM medium containing 10% FCS expressed most of the analyzed protein components. When the same medium, but depleted of ECM proteins by filtrating through a membrane with cut-off at 〉100 kD was used, basal mRNA expression of the ECM proteins was changed in most of the examined cell lines. Using serum free conditions, most of the cell lines again showed a variation in the expression pattern of mRNA encoding for the different ECM proteins compared to the other medium conditions. Comparing different cell lines from one tumor entity or different tumor groups, ECM expression was heterogeneous with regard to the different tumor entities as well as within the entities themselves. Migration assays revealed heterogeneous responses between the different cell lines, ECM components and culture conditions, making it difficult to correlate ECM expression patterns and migratory behavior. Our results revealed that all examined cell lines are able to produce ECM proteins in vitro. This suggests that tumor cells can modulate their microenvironment in vitro which has to be taken into consideration for studies related to migration and invasion.
    Type of Medium: Electronic Resource
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